Division of Gastroenterology, Director of Hepatology, Georgetown University Medical Center, 3800 Reservoir Road, NW Washington, DC 20007, USA.
Expert Rev Gastroenterol Hepatol. 2010 Feb;4(1):13-29. doi: 10.1586/egh.09.72.
Irritable bowel syndrome affects 5-10% of North Americans, with an estimated one-third having a diarrhea-predominant form. Alosetron hydrochloride (Lotronex) is a serotonin receptor type 3 antagonist approved in early 2000 for use in women with diarrhea-predominant irritable bowel syndrome (IBS-D). Initial use was widespread, but infrequent serious adverse events of ischemic colitis and severe constipation-related complications prompted alosetron's voluntary withdrawal from the US market in November 2000. Unprecedented public request prompted its reintroduction in 2002 under a Risk Management Plan, including a more restricted indication and a Prescribing Program for Lotronex. Despite these measures, the use of alosetron has been very limited since its reintroduction. Possible deterrents to its use include concerns over safety and the possible medical-legal implications raised by the Risk Management Plan. It is also possible that changes in the natural history and/or diagnosis of IBS-D have reduced the target population. Given the unique regulatory history of alosetron, these issues continue to engender controversy. This article profiles these concerns and reviews the pharmacology, clinical efficacy and safety, and post-marketing experience with alosetron. Myths and misconceptions related to alosetron use, or lack thereof, are addressed to provide the reader with the evidence needed to make informed treatment decisions for their female patients with severe IBS-D.
肠易激综合征影响北美 5-10%的人群，估计有三分之一的人患有腹泻为主型。盐酸阿洛司琼（Lotronex）是一种 5-羟色胺受体 3 拮抗剂，于 2000 年初获准用于腹泻为主的肠易激综合征（IBS-D）女性患者。最初的使用范围很广，但缺血性结肠炎和严重便秘相关并发症等罕见严重不良事件促使阿洛司琼于 2000 年 11 月自愿从美国市场撤出。前所未有的公众要求促使其在 2002 年根据风险管理计划重新引入，包括更严格的适应证和 Lotronex 处方计划。尽管采取了这些措施，但自重新引入以来，阿洛司琼的使用非常有限。其使用的可能障碍包括对安全性的担忧以及风险管理计划提出的可能的医疗法律影响。也有可能是 IBS-D 的自然病史和/或诊断发生了变化，从而减少了目标人群。鉴于阿洛司琼独特的监管历史，这些问题仍在引发争议。本文介绍了这些关注点，并回顾了阿洛司琼的药理学、临床疗效和安全性以及上市后经验。本文还针对与阿洛司琼使用相关的误解和缺乏使用的情况进行了讨论，旨在为读者提供做出明智的治疗决策所需的证据，以治疗其女性严重 IBS-D 患者。
